To investigate the role and underlying mechanism of spermidine (SPD) in intracerebral hemorrhage (ICH).

Male C57BL/6 mice were subjected to establish a collagenase-induced ICH model. The 108 mice were randomly divided into Sham group, ICH group and ICH+SPD group (intraperitoneal injection of 15 mg/kg SPD for 3 consecutive days after modeling), with 36 mice in each group. On the 3rd day after ICH, neurological deficits were evaluated using modified Garcia scoring and forelimb placing test; brain pathological damage was assessed with HE staining; activation of microglia/macrophages (Iba-1) and astrocytes (GFAP) was detected by immunofluorescence assay; expression of autophagy markers (Beclin-1, P62) and inflammatory factors (MMP-9, NLRP3, COX-2) was measured with Western blotting. In in vitro experiments, hemin was used to stimulate HT-22 cells to mimic ICH. The HT-22 cells were randomly divided into Control group, Hemin group, Hemin+SPD group, and Hemin+SPD+3-methyladenine (3-MA, an autophagy inhibitor) group (n=7). After 24 h of hemin treatment, cell viability was detected with CCK-8 assay, the expression of autophagy-related proteins (LC3-Ⅱ and P62) were detected with Western blotting, and oxidative stress was determined by measuring superoxide dismutase (SOD) activity and malondialdehyde (MDA) content.

On day 3 post-ICH, SPD significantly reduced the area of brain damage (P<0. 05), improved neurological recovery (P<0. 05), activated autophagy with up-regulation of Beclin-1 while down-regulation of P62 (P<0. 05), suppressed the activation of microglia/macrophage and astrocytes (P<0. 01), reduced the expression of MMP-9, NLRP3 and COX-2, and enhanced SOD activity and decreased MDA content (P<0. 05) when compared with the ICH group. SPD increased the viability of HT-22 cells (P<0. 05), improved SOD activity and reduced MDA content (P<0. 01). Autophagy inhibitor 3-MA effectively blocked the down-regulation of LC3-Ⅱ and up-regulation of P62, and completely reversed above protective effects caused by SPD (P<0. 05).

SPD activates autophagy after ICH and improves post-ICH brain injury by suppressing neuroinflammation and oxidative stress.

Intracerebral hemorrhage (ICH) poses a significant global health burden, characterized by high mortality rates and long-term disability. Despite advancements in stroke management, effective therapeutic strategies targeting secondary brain injury mechanisms post-ICH remain elusive. In this study, we explored the neuroprotective potential of edaravone (EDA) in a mouse model of ICH, with particular focus on the innovative approach of intranasal administration.

A total of 96 C57BL/6 mice were randomly assigned to sham group (n = 32), ICH + vehicle group (n = 32) and ICH + EDA group (n = 32). ICH was induced using 0.5 μL bacterial collagenase Ⅶ. EDA (3 mg/kg) was administered intranasally starting 2 h after ICH and every 12 h thereafter (20 μL per mouse; 5 μL per nostril every 5 min). The ICH + vehicle group received the identical solvent at an equivalent volume as the EDA group via intranasal administration. We evaluated neurological functions through mNSS, corner turn, and forelimb placement tests. Additionally, brain water content, immunofluorescence staining, western blot analysis, Evans blue extravasation assay, and TUNEL staining were utilized to examine the neuroprotective effects of EDA in ICH.

Our findings demonstrate that intranasal delivery of EDA significantly alleviated neurological deficits and reduced brain injury following ICH. This was evidenced by improvements in behavioral assessments, decreased brain water content, reduced lesion volume, and diminished cell death in the perihematomal region. Notably, intranasal EDA administration preserved blood-brain barrier integrity, suppressed microglia/macrophage activation, and mitigated oxidative stress, highlighting its multifaceted neuroprotective mechanisms.

These outcomes underscore the therapeutic promise of intranasal administration of EDA as a prospective intervention for alleviating secondary brain injury post-ICH and advocate for further translational and clinical investigations to validate its efficacy and safety in ICH patients.

Intracerebral hemorrhage (ICH) is a major type of stroke associated with high rates of mortality and long-term disability, often leading to inflammation, brain edema, and neuronal loss. Icariin (ICA) is the primary active compound extracted from Herba epimedii, and it possesses several pharmacological effects including anti-inflammatory, antioxidant and anti-apoptotic properties. However, its neuroprotective capacity and mechanisms in ICH remain unknown. This study investigates the neuroprotective potential of ICA in an ICH mouse model.

A total of 108 C57BL/6 mice were randomly assigned to three groups: sham group (n = 36), ICH + vehicle group (n = 36), and ICH + ICA group (n = 36). ICH was induced in the ICH + Vehicle and ICH + ICA groups through injection of collagenase type Ⅶ into the basal ganglia. The ICH + ICA group was administered ICA (60 mg/kg/day) intraperitoneally for three consecutive days. Neurological assessment was conducted using the corner test and modified neurological severity scores. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) staining was performed to evaluate brain cell death. Brain water content, Western blot, Evans blue (EB) dye extravasation, and immunofluorescence staining were conducted 3 days post-ICH.

ICA treatment significantly alleviated brain edema and enhanced neurological function in mice three days post-ICH. Immunofluorescence results revealed that ICA decreased microglia and astrocyte activation and reduced neutrophil infiltration. Western blot results demonstrated that ICA maintained blood-brain barrier (BBB) integrity by decreasing the loss of tight junction proteins, including Occludin and Zonula occludens-1. ICA also lowered matrix metalloproteinase-9 and the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. TUNEL staining showed a reduction in neuronal cell death with ICA, linked to enhanced level of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and reduced expression of the pro-apoptotic Bcl-2-associated X (Bax) protein.

ICA exhibits significant neuroprotective effects in mice following ICH by reducing neuroinflammation, maintaining BBB integrity, and attenuating brain cell death.

To evaluate the efficacy and safety of combining troxerutin and cerebroprotein hydrolysate (TCH) for treating acute cerebral infarction via a systematic review.

The computer-based search encompassed eight databases—PubMed, Cochrane Library, Embase, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data, and China Science and Technology Journal Database—from their establishment until December 2023. Randomized controlled trials that assessed TCH for acute cerebral infarction were selected according to inclusion and exclusion criteria. The data extraction, data quality evaluation, and meta-analysis were performed using RevMan 5.4.1 software.

The analysis incorporated 18 studies encompassing 1,957 cases. Compared with the control group, the TCH treatment group had superior outcomes in effective rates (risk ratio [RR] = 1.24, 95% confidence interval [CI; 1.18, 1.30], Z = 8.84, p < 0.05), neurological deficit scores (mean difference [MD] = −3.71, 95% CI [−4.32, −3.10], Z = 11.92, p < 0.05), activity of daily living scores (MD = 13.32, 95% CI [11.66, 14.98], Z = 15.75, p < 0.05), changes in low shear viscosity (MD = −1.82, 95% CI [−2.57, −1.06], Z = 4.73, p < 0.05), and plasma fibrinogen levels (MD = −0.43, 95% CI [−0.47, −0.39], Z = 20.01, p < 0.05). However, there was no significant difference in adverse reaction between the two groups (RR = 0.72, 95% CI [0.45, 1.14], Z = 1.39, p = 0.16). No severe adverse drug reactions were observed in either group.

Combined TCH is effective and safe for treating acute cerebral infarction.